Progressive symmetrical erythrokeratoderma associated with biallelic PNPLA1 variants.

Jiang, Xingyuan; Echeandia-Francis, Caroline; Mani, Mitra V; Hyden, Martin; Lange-Asschenfeldt, Bernhard; Hügel, Rainer; Hausser, Ingrid; Süßmuth, Kira et al. · Br J Dermatol · 2026

case_series · Level IV

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Abstract

We describe three kindreds with progressive symmetrical erythrokeratoderma associated with recessive <i>PNPLA1</i> variants, expanding the clinical spectrum of patatin-like phospholipase domain-containing protein 1 (PNPLA1)-related epidermal differentiation disorders. Affected individuals exhibited distinctive symmetrical plaques with patterned sparing, contrasting with the generalized scaling typical of <i>PNPLA1</i>-associated autosomal recessive congenital ichthyosis. These findings highlight genotype–phenotype variability within PNPLA1 disease and support a role for lipid pathway-specific modifiers in shaping epidermal differentiation disorder phenotypes.